Significance: Dynamic diffuse fluorescence tomography (DFT) can recover the static distribution of fluorophores and track dynamic temporal events related to physiological and disease progression. Dynamic imaging indocyanine green (ICG) approved by the food and drug administration is still under-exploited because of its characteristics of low quantum yield and relatively rapid tissue metabolism.
Aim: In order to acquire the ICG tomographic image sequences for pharmacokinetic analysis, a dynamic DFT system was proposed.
Approach: A fiber-based dynamic DFT system adopts square-wave modulation lock-in photon-counting scheme and series-parallel measurement mode, which possesses high sensitivity, large dynamic range, high anti-ambient light ability in common knowledge, as well as good cost performance. In order to investigate the effectiveness of the proposed system, the measurement stability and the anti-crosstalk—a crucial factor affecting the system parallelization—were assessed firstly, then a series of static phantoms, dynamic phantoms and in vivo mice experiments were conducted to verify the imaging capability.
Results: The system has the limited dynamic range of 100 dB, the fluctuation of photon counting within 3%, and channel-to-channel crosstalk ratio better than 1.35. Under the condition of a sufficient signal-to-noise ratio, a complete measurement time for one frame image was 10.08 s. The experimental results of static phantoms with a single target and three targets showed that this system can accurately obtain the positions, sizes, and shapes of the targets and the reconstructed images exhibited a high quantitativeness. Further, the self-designed dynamic phantom experiments demonstrated the capability of the system to capture fast changing fluorescence signals. Finally, the in vivo experiments validated the practical capability of the system to effectively track the ICG metabolism in living mice.
Conclusions: These results demonstrate that our proposed system can be utilized for assessing ICG pharmacokinetics, which may provide a valuable tool for tumor detection, drug assessment, and liver function evaluation.
Fluorescence pharmacokinetics can analyze the absorption, distribution, metabolism and other pharmacokinetic processes of fluorescence agents in biological tissues over time, which can provide more specific and quantitative physiological and pathological information for the evaluation of organ function. This paper is devoted to studying pharmacokinetics of indocyanine green (ICG) in healthy mice and mice with acute alcoholic liver injury based on a home-made dynamic diffuse fluorescence tomography system that possesses high sensitivity and large dynamic measurement range on account of digital lock-in-photon-counting technique. In this study, four-week-old Kunming mice were randomly divided into experimental and control groups. The time-varying distribution of ICG in mice was obtained by diffuse fluorescence tomography reconstruction, and the pharmacokinetic parameters were further extracted from the ICG concentration-time curve. The results showed that the dynamic diffuse fluorescence tomography system successfully captured the ICG metabolism process in mouse liver, and the ICG excretion rate demonstrated an obvious difference between healthy mice and the mice with acute alcoholic liver injury.
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